Designing Darwin’s Finches

Cheng-Ming Chuong, professor of pathology in USC’s Keck School of Medicine.Credit: USC

The shapes of bird beaks in a developing embryo are associated with a specific protein, according to researchers from the Keck School of Medicine of USC.

A paper to be published in this week’s issue of the journal Science describes the molecular process involving bone morphogenetic protein 4 (BMP4). A report on this paper and another closely related study will appear in the journal’s news section.

Different bird species tend to have differently shaped beaks, which are said to reflect the different evolutionary pressures under which they develop.

In fact, Charles Darwin looked to 13 different species of finches from the Galapagos Islands to help bolster his theories of evolution, showing that while the Galapagos finches most likely had descended from a common ancestor, they had developed into distinct species based on differences in their beaks – differences which corresponded with their confinement to different islands in the archipelago and their adaptation to different ecological niches.

Today, beak shape is considered "a classical example of evolutionary diversification," wrote Cheng-Ming Chuong, principal investigator on the Science paper and professor of pathology in the Keck School of Medicine, along with his colleagues.

Still, while the reason for this diversity is explained by evolutionary selection, little is known about how different beak shapes are built at the cellular and molecular level.

"Since beaks are made from cells, each ‘designer beak’ must be made through differences in the regulation of cell behaviors," Chuong noted.

Beaks are actually a collection of "facial prominences," Chuong said, and these prominences grow at varying rates during chick development to "compose a unique beak." But while early chicken beak development has been studied to some degree, little is known about how these shapes are created in the later stages of development.

The biomolecule, DNA, that twists throughout the cell nucleus

To shed some light on that question, Chuong and colleagues compared beak development in chickens and ducks: Duck beaks are long and wide, Chuong noted, while chicken beaks are small and have a conical shape. In their studies, the researchers focused on one particular facial prominence called the frontonasal mass, or FNM.

Research associate Ping Wu, the paper’s first author, found that in chickens and ducks there are two areas in the developing FNM in which cells divide rapidly to create the beak’s mass.

In chickens, those two areas gradually converge into one area on the distal end of the beak, creating a sharp, growing tip. In ducks, two such proliferative zones remain, creating a wider, bigger beak.

Using in situ hybridization techniques, the researchers tracked the levels of a number of growth-related genes. They were able to pinpoint BMP4 as a candidate for mediating growth, Chuong said.

In humans, several BMPs play a role in enhancing the rates of cell division and growth and regulating major developmental events including bone differentiation. Deregulation of BMP pathway activity has also been linked to some tumor growth.

To test whether BMP4 is indeed a growth mediator, they used techniques from gene therapy and protein delivery to mis-express BMP4 and its antagonist.

"The results," Chuong said, "were astounding. The chicken beaks were modulated into a spectrum of beak shapes mimicking those seen in nature."

An accompanying paper in Science, which looked at molecular differences among the Galapagos finches themselves, also identified BMP4 as a major mediator of beak shape in a variety of finch species.

Charles Darwin (1809-1882) "No breeder doubts how strong is the tendency to inheritance: like produces like…"

Together, these two studies are able to point to BMP4 as having a major role in the creation of the avian beak, demonstrating that it is "one of the major driving forces building beak mass."

By tinkering with BMP4 in beak prominences, Chuong and his scientific colleagues wrote, "the shapes of the chicken beak can be modulated."

"These two papers in Science represent a major step in basic biology," Chuong said, "moving toward a molecular understanding of Darwin’s evolutionary theories. The principles learned here also have practical implications. Learning how nature molds stem cells into specific organs will help scientists make progress in tissue engineering."

The next step, Chuong said, is to look into how these areas of cell proliferation are localized physiologically, "an issue that’s also of concern to cancer research.". In addition, he and his colleagues will be trying to understand how BMP4 and other morphogenetic molecular activities are regulated to adapt to environmental changes.

The work in the Science paper was supported by grants from the National Institutes of Health.